Submissions for variant NM_000051.4(ATM):c.3279_3282del (p.Asn1094fs)

dbSNP: rs879254281

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236873	SCV000294048	likely pathogenic	not provided	2016-03-14	criteria provided, single submitter	clinical testing	This apparently mosaic deletion of 4 nucleotides in ATM is denoted c.3279_3282delCAAT at the cDNA level and p.Asn1094AspfsX14 (N1094DfsX14) at the protein level. The normal sequence, with the bases that are deleted in braces, is CAAT{CAAT}AGgt. The deletion causes a frameshift which changes an Asparagine to an Aspartic Acid at codon 1094, and creates a premature stop codon at position 14 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Invitae	RCV001389763	SCV001591216	pathogenic	Ataxia-telangiectasia syndrome	2023-06-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 246478). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1094Aspfs*14) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).
Ambry Genetics	RCV002321907	SCV002606499	pathogenic	Hereditary cancer-predisposing syndrome	2021-05-10	criteria provided, single submitter	clinical testing	The c.3279_3282delCAAT pathogenic mutation, located in coding exon 21 of the ATM gene, results from a deletion of 4 nucleotides at nucleotide positions 3279 to 3282, causing a translational frameshift with a predicted alternate stop codon (p.N1094Dfs*14). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.